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Environmental Pollution


Perfluorooctanesulfonic acid (PFOS) is a ubiquitous environmental contaminant, previously 16 utilized as a non-stick application for consumer products and firefighting foam. It can cross the 17 placenta, and has been repeatedly associated with increased risk for diabetes in epidemiological 18 studies. Here, we sought to establish the hazard posed by embryonic PFOS exposures on the 19 developing pancreas in a model vertebrate embryo, and develop criteria for an adverse outcome 20 pathway (AOP) framework to study the developmental origins of metabolic dysfunction. 21 Zebrafish (Danio rerio) embryos were exposed to 16, 32, or 64 μM PFOS beginning at the mid-22 blastula transition. We assessed embryo health, size, and islet morphology in Tg(insulin-GFP) 23 embryos at 48, 96 and 168 hpf, and pancreas length in Tg(ptf1a-GFP) embryos at 96 and 168 24 hpf. QPCR was used to measure gene expression of endocrine and exocrine hormones, digestive 25 peptides, and transcription factors to determine whether these could be used as a predictive 26 measure in an AOP. Embryos exposed to PFOS showed anomalous islet morphology and 27 decreased islet size and pancreas length in a U-shaped dose-response curve, which resemble 28 congenital defects associated with increased risk for diabetes in humans. Expression of genes 29 encoding islet hormones and exocrine digestive peptides followed a similar pattern, as did total 30 larval growth. Our results demonstrate that embryonic PFOS exposures can disrupt pancreatic 31 organogenesis in ways that mimic human congenital defects known to predispose individuals to 32 diabetes; however, future study of the association between these defects and metabolic 33 dysfunction are needed to establish an improved AOP framework.


This article has been accepted for publication in Environmental Pollution